Mesenchymal Stem Cell Administration in the Treatment of Coronary Graft Disease in Heart Transplant Patients (MESHT)

February 20, 2017 updated by: Assistance Publique - Hôpitaux de Paris

MES-HT is a pilot multicenter prospective study conducted in transplant patients who developed severe coronary vasculopathy. A preparation of autologous mesenchymal cells of bone marrow is administered by endomyocardial injection, guided by the Noga® cardiac mapping system.

The main objective is to determine the effect of the administration of autologous mesenchymal cells of the bone marrow by intramyocardial injection on myocardial perfusion in cardiac transplant patients with severe coronary vasculopathy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Suspended

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

MES-HT is a phase 1-2 multicenter pilot prospective study conducted on 14 heart transplant patients who developed severe coronary vasculopathy, in the aim to assess the effect on myocardial perfusion of the intramyocardial administration by percutaneous way of autologous mesenchymal stem cells derived from the bone marrow.

The main objective is to show improvement in myocardial perfusion in a non-randomized and uncontrolled pilot study, before considering a randomized controlled study. The administration of intra myocardial cells using the NOGA system was carried out to date with more than 1,000 patients and is considered feasible and safe. However, the investigators will assess very carefully the feasibility and safety of this invasive approach.

The primary endpoint is the improvement of myocardial perfusion measured by MRI after endomyocardial injection of mesenchymal cells by percutaneous way, guided by the NOGA system.

The secondary endpoints are the feasibility and safety of this administration, changes in ejection fraction measured by contrast echocardiography, changes in other MRI cardiac parameters (left ventricular volumes , intramyocardial fibrosis), the oxygen consumption during exercise, myocardial perfusion measured by SPECT. Other secondary endpoints are the evolution of the immune status, and histological criteria of myocardial biopsy.

Once the mapping performed, preparation is injected through another catheter (MYOSTAR injection catheter) which will also be guided by the Noga® system. This catheter may be positioned on the regions of interest (viable ischemic areas) and allow the injection of the quantity of CSM (40 million / ml) in 10 to 12 different injection points and injection volumes 0.3 ml for a total dose of 120 to 144 million cells.

After each injection procedure, patients are monitored for 48 hours minimum clinically and under continuous ECG monitoring to detect possible arrhythmias. A troponin dosage is done after 6 H, and after 24 and 48 hours. An echocardiogram is performed immediately after the procedure and before the release to 48 H.

A clinical evaluation will be made after the patient is discharged at 1 month (clinical examination + Holter + echocardiography), 3 months (examination), 6 months (clinical examination, Holter, echocardiography, cardiac MRI, test of effort with measurement of VO2, effort myocardial tomoscintigraphy and for patients from Pitie-Salpetriere hospital, Rubidium 82 by positron emission tomography) and 12 months (examination). Myocardial biopsy and a control coronary angiography will be only performed within 12 months in accordance with the practice of the teams.

Patients will benefit from a biological monitoring which provides for the monitoring of immune response. This immuno-monitoring is to assess the possible influence of the injection of mesenchymal cells on immunological tolerance mechanisms. It will be implemented in the balance sheets of cardiac tissue at the waning annual biopsies and peripheral blood samples on inclusion, 48 hours after injection and at 1 month, 3 months and 6 months.

The limiting toxicity is defined as the occurrence at one month of a serious adverse effect related to the protocol , requiring an hospitalization or being able to be life-threatening , or like abundant pericardial effusion requiring pericardial drainage, bleeding complications requiring blood cell transfusion or surgery, stroke constituted, sepsis or septic shock, cardiogenic shock, severe ventricular rhythm refractory death.

All patients are followed for one year.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75013
        • Département de cardiologie du Pr Michel KOMADJA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria :

  1. Cardiac transplant patient whatever is his initial pathology

  2. Coronary vasculopathy grade 3 (CAV3) defined by:

    Stenosis > 50% of common-core (CT) or stenosis >70% of at least 2 or 3 main coronary arteries or stenosis > 70% on secondary branches of 3 territories.

    Coronary vasculopathy grade 1 or 2 (CAV 1 or 2) associated with FELV (FEVG) dysfunction <45% or abnormality of completion of restrictive type.

  3. Defect of drip on at least 2 segments/17 in stress MRI.
  4. Fraction of ejection LV<50 measured on ultrasound examination or confusion of diastolic function defined by a restrictive mitral steam (E/A > 2 or E/A between 1 and 2 and deceleration time E < 150 ms) or left ventricular diastolic pressure measured during coronarography >16mg Hg .
  5. Without sign of acute rejection at the time of inclusion.
  6. Under an optimal medical treatment
  7. Patient who have given his enlightened and signed consent

Exclusion criteria :

  1. Patients <18 ou >80 years
  2. Acute coronary syndrome or revascularisation in the 3 last months
  3. Acute cardiac rejection in the 3 last months
  4. Atrial fibrillation
  5. Claustrophobia or contraindication to MRI (ex:pace-maker), to contrast injection or adenosine.
  6. Presence of a thrombus in the left cavities detected by ultra-sound examination or MRI realized before the injection..
  7. Pregnant or breast-feeding woman
  8. Woman old enough to reproduction without effective means of contraception during its participation in the study
  9. Patient benefiting from a legal protective measure
  10. HIV positive
  11. Not membership in a national save insurance (beneficiary or legal successor)
  12. Patients undergoing others biomedical research
  13. Patient not understanding the procedure bound to the protocol
  14. Bad adhesion to the protocol suspected by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Mesenchymal cell therapy
Biological: Mesenchymal cell therapy

Name of the experimental cell preparation: Concentrated mesenchymal stem cells (MSCs) derived from autologous bone marrow

  • Registry Type: autologous
  • Qualitative and quantitative composition of the finished product: The product is a cell suspension consisting of mesenchymal stem cells (MSC) 40 x 106 MSC / ml suspended in human albumin (ALBUNORM ® 5% OCTAPHARMA France).
  • Route of administration: endomyocardial injection
  • Dose administered: 120-140 x106 MSC (mesenchymal stem cells)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
myocardial perfusion measured in MRI.
Time Frame: 6 months
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
complications of catheterization
Time Frame: 6 months
6 months
complications of endomyocardial injection
Time Frame: 6 months
6 months
systolic function
Time Frame: 6 months
6 months
diastolic function
Time Frame: 6 months
6 months
immunomodulation induced MSCs in the blood
Time Frame: 6 months
6 months
immunomodulation induced MSCs in myocardial biopsy
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Richard Isnard, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2014

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 1, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 10, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 15, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 23, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 20, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P 100102

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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